Much of the present understanding of the oculomotor system has evolved rom morphological, physiological, and clinicopathological studies of the neurones and pathways that are related to various types of eye movement. The overall objective of this research is to elucidate the structural organization of the oculomotor system in relation to the neurotransmitters that are utilized by premotor neurones and the changes that accompany lesions of premotor pathways and the motor nerves. The major emphasis of the proposed studies will be to characterize the putative excitatory and inhibitory neurotransmitters of premotor neurones to the oculomotor, trochlear, and abducens nuclei by light and electron microscopy using autoradiographic and immunohistochemical techniques. These findings will for a basis for the examination of structural changes in trochlear motoneurones and their synaptic inputs following IVth nerve axotomy. Utilizing light and electron microscopic histochemical and immunohistochemical techniques, these studies will assess the role of intrinsic versus extrinsic factors that are correlated with the phenomenon of motoneurone survival and death following axotomy. The effects of lesions of the medial longitudinal fasciculus will be examined by light and electron microscopy in relation to not only the target motoneurones in the oculomotor and trochlear nuclei, but also the morphology of muscle fibers in the extraocular muscles. These studies will assess the trophic role of the presynaptic inputs in maintaining the structural integrity of the motoneurones and their relation to the different muscle fiber types that are innervated by the motoneurones. The specific aims of this research are consistent with the long-term goal of understanding the neuronal and synaptic organization of the oculomotor system underlying the control of gaze and the sequellae, both central and peripheral, of neurological disorders that are characterized by deficits in ocular motility.